A Rare Case of Coexisting Breast Cancer and Refractory Acute Myeloid Leukemia.

The occurrence of acute myeloid leukemia (AML) within six months from a diagnosis of breast cancer (BC) is rarely reported in the literature, and it is associated with a poor prognosis. We report herein the case of a 40-year-old woman referred to our centre affected by BC and simultaneous AML. The patient proved refractory to first line therapy and achieved complete remission (CR) with a clofarabine-based regimen followed by allogeneic stem cell transplantation (ASCT). Both during salvage chemotherapy and after ASCT, the patient presented severe infectious complications ( acute cholecistytis and Nocardia pneumonia, respectively) treated with surgery, and currently she is alive in CR for both diseases after 29 months of follow-up. The case highlights the importance of a diagnostic assessment of any unexplained cytopenia in association with solid neoplasia under treatment, underlining the feasibility and priority of a timely treatment of the haematological neoplasm in order to achieve long-term survival.

Complete remission obtained with azacitidine in a patient with concomitant therapy related myeloid neoplasm and pulmonary mucormycosis.

Mucormycosis is the third cause of invasive mycosis after candidiasis and aspergillosis in AML patients, representing a poor prognostic factor associated with a high rate of fatal outcome. We report a case of a patient with AML and a concomitant pulmonary mucormycosis at diagnosis, who obtained a complete remission both of her AML and of the fungal infection. The incidence of the infection at the onset of leukemia is extremely unusual, and, to our knowledge, the sporadic cases reported in the literature are included in heterogeneous series retrospectively examined. In our case, Liposomal Amphotericin B as single agent appeared incapable of controlling the infection, so anti-infective therapy was intensified with posaconazole and simultaneously antileukemic treatment with 5-azacitidine was started, with the understanding that the only antifungal treatment would not have been able to keep the infection under control for a long time if not associated with a reversal of neutropenia related to the disease. We observed a progressive improvement of the general conditions, a healing of pneumonia and a complete remission of the leukemic disease, suggesting that a careful utilization of the new compounds available today, in terms of both antifungal and antileukemic treatment, may offer a curative chance a patient who would have otherwise been considered unfit for a potentially curative therapeutic strategy.

ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS-13 deficiency, both during the acute episode and remission, is a well-established predictor of recurrence. The predictive value of anti-ADAMTS-13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. OBJECTIVES: To analyze ADAMTS-13-related biomarkers (ADAMTS-13 and anti-ADAMTS-13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. PATIENTS/METHODS: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. RESULTS: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS-13 activity or antigen levels (<10%), the presence of ADAMTS-13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. CONCLUSIONS: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS-13-related parameters during remission is warranted.

How long can we give interleukin-2? Clinical and immunological evaluation of AML patients after 10 or more years of IL2 administration.

We have treated 20 patients, affected by acute myelogenous leukemia in advanced phase of the disease, with intravenous high-dose recombinant interleukin-2 (IL2) as induction treatment, achieving a complete remission (CR) in 11/20 of patients (55%). All CR patients were planned to receive a maintenance program with lower subcutaneous doses of IL2 until relapse. Currently, 5/11 patients are alive in continuous complete remission with a minimum follow-up of 9 years from IL2 induction. In the aim to investigate the treatment's side-effects during or after prolonged IL2 therapy, we decided to submit these patients to a clinical and immunological evaluation. Four patients have been evaluated as one, who independently stopped IL2 after 6 years, refused the check-up. No organ-specific treatment sequelae that may decrease the quality of life or may be life-threatening were found, concerning renal, liver and cardiovascular function. Endocrine abnormalities were detected in three patients, the most serious being a severe hypothyroidism, which prompted cessation of IL2 maintenance after 6 years and required thyroid supplementation treatment. Immunological studies were carried out prior to the last IL2 cycle and showed high levels of CD3-positive T cells expressing the IL2 receptor alpha chain (CD25), both in the peripheral blood and in the bone marrow. Our study shows that low-dose IL2 can be given for a prolonged period of time without serious organ-specific late sequelae and with a good quality of life.

Thrombotic thrombocytopenic purpura: prospective neurologic, neuroimaging and neurophysiologic evaluation.

BACKGROUND AND OBJECTIVES: Neurologic symptoms are present in 60% of patients with thrombotic thrombocytopenic purpura (TTP) on initial examination and ultimately develop in about 90% of cases during the course of the disease. Despite central nervous system involvement being frequent, abnormalities in the brain of patients with TTP are infrequent on neuroimaging (CT/MRI) and neurophysiologic (EEG) evaluation, often reversible and mainly limited to symptomatic stages of the disease. The aim of our study was to establish the value of a complete neurologic screening as part of the work up of TTP. DESIGN AND METHODS: We prospectively evaluated 16 TTP patients, performing serial neurologic, neuroimaging and EEG examinations, independently of the presence of an objective central nervous system involvement. RESULTS: Our study shows that a complete neurologic evaluation is of modest help in improving the diagnosis of TTP, but may be useful for the neurologic management. INTERPRETATION AND CONCLUSIONS: Accurate neuroimaging and, especially, EEG evaluation and monitoring allowed us to identify patients who could benefit from anticonvulsive therapy, avoiding the unnecessary administration of the latter. The prognostic utility of complete neurologic screening in TTP remains to be conclusively demonstrated in larger prospective neurologic studies.

Obesity and autologous stem cell transplantation in acute myeloid leukemia.

In the bone marrow transplant setting, several authors hypothesized that severely overweight patients are at increased risk of transplant-related toxicity, but different definitions of obesity, different body weight groupings and heterogeneous samples of patients were analyzed. To overcome these limitations, we retrospectively considered a homogeneous group of 54 patients (median age 36.5 years), with a diagnosis of de novo acute myeloid leukemia (AML), autografted in first complete remission (CR) with the Bu-Cy2 conditioning regimen, dosed on actual body weight. Patients were classified into three groups (obese, non-obese, underweight) using body mass index (BMI = kg/m(2)); for each group we analyzed transplant-related toxicity and mortality, overall survival and disease-free survival (OS/DFS). In spite of the relatively small number of patients, in our results high BMI appears a predictive factor for an increase of treatment-related toxicity and mortality. Moreover, 30 (55%) patients are currently alive in continuous CR, and after a median follow-up of 76.5 months (range 14-137) statistically significant differences in OS and DFS were detected between obese and non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests that obesity may represent an independent risk factor for autograft in AML and further investigations are warranted.

High-dose idarubicine, busulphan and melphalan as conditioning for autologous blood stem cell transplantation in multiple myeloma. A feasibility study.

Extensive studies have tested the clinical impact of double and triple sequential transplants as front-line therapy in MM, following the suggestion that dose escalation can overcome the marked drug resistance characteristic of this disease, but the superiority of such approaches vs one single transplant has still to be demonstrated. The aim of our study was to evaluate the feasibility and efficacy of high-dose idarubicine intensification of a standard busulphan-melphalan conditioning regimen in MM. Twenty-eight patients (median age 55 years) with sensitive disease received PBSCT after high-dose idarubicine combined with busulphan and melphalan and followed by s.c. rhG-CSF until PMN recovery. The most severe toxicity was represented by oral mucositis which resolved with hemopoietic reconstitution. Overall response and CR rate were 52% and 40%, respectively. Currently, 36 patients are alive and 19 are progression-free a median of 20 months (12-36) from transplant. The 3-year projected probability of progression-free survival for patients transplanted after first-line treatment is 60%. The combination of Ida/Bu/Melph appears a promising alternative regimen for PBSCT in myeloma, with low transplant-related toxicity and fast hematological recovery. Long-term follow-up and a prospective randomized study, now ongoing, will probably clarify whether an idarubicine-intensified regimen will result in superior outcomes to conventional conditioning and even be comparable to a double consecutive transplant program.